Neuromuscular blocking effects of cisatracurium and its antagonism with neostigmine in a canine model of autosomal-recessive centronuclear myopathy

Br J Anaesth. 2015 Dec;115(6):927-31. doi: 10.1093/bja/aev397.


Background: Centronuclear myopathy (CNM) is a rare congenital condition associated with skeletal muscle weakness. Patients with CNM may have decreased acetylcholine receptor expression and a reduced number of releasable quanta. Such perturbations could affect the time-course of neuromuscular blocking agents (NMBAs) and their antagonism with cholinesterase inhibitors. As a result of the rarity of CNM, prospective data regarding NMBA use in this subpopulation is scarce. We evaluated the neuromuscular blocking effects of cisatracurium and its antagonism with neostigmine in a canine model of CNM.

Methods: Six dogs with congenital autosomal-recessive CNM and six controls received cisatracurium 0.15 mg kg(-1) i.v. under general anaesthesia and intermittent positive pressure ventilation. Neuromuscular function was monitored with acceleromyography.When the second response (T2) to train-of-four (TOF) stimulation returned, neostigmine 0.04 mg kg(-1) (with glycopyrrolate) were administered i.v. The onset time, time to spontaneous return of T2, and the time to reach a TOF ratio ≥0.9 after neostigmine administration were recorded.

Results: Onset time was no different between groups. Median (interquartile range) time to return of T2 was 27 (24-31) min for control dogs and 26 (22-31) min for CNM dogs (P=0.93).After neostigmine administration, a TOF ratio ≥0.9 was reached in 12 (10-15) min and 17 (16-19) min in control and CNM, respectively (P=0.005).

Conclusions: The spontaneous return of T2 was not different between groups. However, neostigmine-facilitated recovery was significantly slower in dogs with CNM. Canine autosomal-recessive CNM does not preclude the use of cisatracurium or its antagonism with neostigmine.

Keywords: myotubular myopathy; neuromuscular nondepolarizing agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia Recovery Period
  • Anesthesia, General / methods
  • Animals
  • Atracurium / analogs & derivatives*
  • Atracurium / antagonists & inhibitors
  • Atracurium / pharmacology
  • Cholinesterase Inhibitors / pharmacology
  • Disease Models, Animal
  • Dogs
  • Monitoring, Intraoperative / methods
  • Myopathies, Structural, Congenital / physiopathology*
  • Neostigmine / pharmacology*
  • Neuromuscular Blockade / methods
  • Neuromuscular Blocking Agents / antagonists & inhibitors
  • Neuromuscular Blocking Agents / pharmacology*
  • Neuromuscular Junction / drug effects*
  • Neuromuscular Junction / physiopathology


  • Cholinesterase Inhibitors
  • Neuromuscular Blocking Agents
  • Atracurium
  • Neostigmine
  • cisatracurium

Supplementary concepts

  • Myopathy, Centronuclear, Autosomal Recessive